Low-scale phosphoproteome analyses identify the mTOR effector p70 S6 kinase 1 as a specific biomarker of the dual-HER1/HER2 tyrosine kinase inhibitor lapatinib (Tykerb®) in human breast carcinoma cells

Annals of Oncology

Volumn 19, Issue 6, 2008, Pages 1097-1109

  Vazquez Martin, A ^a,b,c   Oliveras Ferraros, C ^a,b,c   Colomer, R ^d   Brunet, J ^a,b,c   Menendez, J A ^a,b,c  

^a CATALAN INSTITUTE OF ONCOLOGY   (Spain)

^b GIRONA BIOMEDICAL RESEARCH INSTITUTE IDIBGI   (Spain)

^c HOSPITAL JOSEP TRUETA   (Spain)

^d MD ANDERSON CANCER CENTER   (Spain)

Author keywords

Breast cancer; HER2; Lapatinib; mTOR; Proteomics; Rapamycin; Tyrosine kinases

Indexed keywords

BIOLOGICAL MARKER; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GLYCOGEN SYNTHASE KINASE 3; LAPATINIB; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 12; MITOGEN ACTIVATED PROTEIN KINASE 3; PROTEIN KINASE B; PROTEIN P90; PROTEIN TYROSINE KINASE INHIBITOR; RAPAMYCIN; RETROVIRUS VECTOR; S6 KINASE; S6 KINASE 1; STRESS ACTIVATED PROTEIN KINASE 1; SYNAPTOPHYSIN; TRASTUZUMAB;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CARCINOMA; CANCER RESISTANCE; CELL SPECIFICITY; CELL STRAIN MCF 7; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; CORRELATION ANALYSIS; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG POTENTIATION; DRUG SENSITIVITY; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; GENE AMPLIFICATION; GENETIC TRANSDUCTION; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN MICROARRAY; PROTEOMICS; QUANTITATIVE ANALYSIS;

ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CELL LINE, TUMOR; DRUG RESISTANCE; FEMALE; HUMANS; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; PROTEOME; PROTEOMICS; QUINAZOLINES; RECEPTOR, ERBB-2; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; TUMOR MARKERS, BIOLOGICAL;

EID: 44849142704     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdm589     Document Type: Article

References (60)

1. Slamon DJ, Clark GM, Wong SG et al. Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235: 177-182.
2. Hynes NE, Stern DF. The biology of erbB-2/neu/HER-2 and fts role in cancer. Biochim Biophys Acta 1994; 1198: 165-184.
3. Neve RM, Lane HA, Hynes NE. The role of overexpressed HER2 in transformation. Ann Oncol 2001; 12 (Suppl 1): S9-S13.
4. Yarden Y. Biology of HER2 and its importance in breast cancer. Oncology 2001; 61 (Suppl 2): 1-13.
5. Rubin I, Yarden Y. The basic biology of HER2. Ann-Oncol 2001; 12 (Suppl 1): S3-S8.
6. Menard S, Pupa SM, Campiglio M, Tagliabue E. Biological and therapeutic role of HER2 in cancer. Oncogene 2003; 22: 6570-6578.
7. Bernard-Marty C, Lebrun F, Awada A, Piccart MJ. Monoclonal antibody-based targeted therapy in breast cancer: Current status and future directions. Drugs 2006; 66: 1577-1591.
8. Agrawal A, Gutteridge E, Gee JM et al. Overview of tyrosine kinase inhibitors in clinical breast cancer. Endocr Relat Cancer 2005; 12 (Suppl 1): S135-S144.
9. Lin NU, Winer EP. New targets for therapy in breast cancer: Small molecule tyrosine kinase inhibitors. Breast Cancer Res 2004; 6: 204-210.
10. Hynes NE, Lane HA. ErbB receptors and cancer: The complexity of targeted inhibitors. Nat Rev Cancer 2005; 5: 341.
11. Carter P, Presta L, Gorman CM et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 1992; 89: 4285-4289.
12. Carter P, Fendly BM, Lewis GD, Sliwkowski MX. Development of Herceptin. Breast Dis 2000; 11: 103-111.
13. Harries M, Smith I. The development and clinical use of trastuzumab (Herceptin). Endocr Relat Cancer 2002; 9: 75-85.
14. Nathta R, Esteva FJ. HER-2-targeted therapy: Lessons learned and future directions. Clin Cancer Res 2003; 9: 5078-5084.
15. Lan KH, Lu CH, Yu D. Mechanisms of trastuzumab resistance and their clinical implications. Ann N Y Acad Sci 2005; 1059: 70-75.
16. Nahta R, Yu D, Hung MC et al. Mechanisms of disease: Understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 2006; 3: 269-280.
17. Nahta R, Esteva FJ. Herceptin: Mechanisms of actions and resistance. Cancer Lett 2006; 232: 123-138.
18. Xia W, Mullin RJ, Keith BR et al. Anti-tumor activity of GW572016: A dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene 2002; 21: 6255-6263.
19. Burris HA III. Dual kinase inhibition in the treatment of breast cancer: initial experience with the EGFR/ErbB-2 inhibitor lapatinib. Oncologist 2004; 9 (Suppl 3): 10-15.
20. Johnston SR, Leary A. Lapatinib: A novel EGFR/HER2 tyrosine kinase inhibitor for cancer. Drugs Today (Barc) 2006; 42: 441-453.
21. Xia W, Gerard CM, Liu L et al. Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells. Oncogene 2005; 24: 6213-6221.
22. Konecny GE, Pegram MD, Venkatesan N et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res 2006; 66: 1630-1639.
23. Spector NL, Xia W, Burris H III et al. Study of the biologic effects of lapatnib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies. J Clin Oncol 2005; 23: 2502-2512.
24. Xia W, Bacus S, Hedge P et al. A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer. Proc Natl Acad Sci USA 2006; 103: 7795-7800.
25. Xia W, Bisi J, Strum J et al. Regulation of survivin by ErbB2. signaling: Therapeutic implications for ErbB2-overexpressing breast cancers. Cancer Res 2006; 66: 1640--1647.
26. Wang SE, Narasanna A, Perez-Torres M et al. HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors. Cancer Cell 2006; 10: 25-38.
27. Xia W, Husain I, Liu L et al. Lapatinib antitumor activity is not dependent upon phosphatase and tensin homologue deleted on chromosome 10 in ErbB2-overexpressing breast cancers. Cancer Res 2007; 67: 1170-1175.
28. Hinow P, Wang SE, Arteaga CL, Webb GF. Relocating job wise? A mathematical model separates quantitatively the cytostalic and cytotoxic effects of a HER2 tyrosine kinase inhibitor. Theor Biol Med Model 2007; 4: 14.
29. Scaltriti M, Rojo F, Ocana A et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst 2007; 99: 628-638.
30. Hegde PS, Rusnak D, Bertiaux M et al. Delineation of molecular mechanisms of sensitivity to lapatinib in breast cancer cell lines using global gene expression profiles. Mol Cancer Ther 2007; 6: 1629-1640.
31. Shamji AF, Nghiem P, Schreiber SL. Integration of growth factor and nutrient signaling: Implications for cancer biology. Mol Cell 2003; 12: 271-280.
32. Fingar DC, Blenis J. Target of rapamycin (TOR): An integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 2004; 23: 3151-3171.
33. Noh WC, Mondesire WH, Peng J et al. Determinants of rapamycin sensitivity in breast cancer cells. Clin Cancer Res 2004; 10: 1013-1023.
34. Bjomsti M-A, Houghton PJ. The TOR pathway: A target for cancer therapy. Nat Rev Cancer 2004; 4: 335-348.
35. Holz MK, Blenis J. Identification of S6 kinase 1 as a novel mammalian target of rapamycin (mTOR)-phosphorylating kinase. J Biol Chem 2005; 280: 26089-26093.
36. Wing LY, Chen HM, Chuang PC et al. The mammalian target of rapamycin-p70 ribosomal S6 kinase but not phosphatidylinositol 3-kinase-Akt signaling is responsible for fibroblast growth factor-9-induced cell proliferation. J Biol Chem 2005; 280: 19937-19947.
37. Hynes NE, Boulay A. The mTOR pathway in breast cancer. J Mammary Gland Biol Neoplasia 2006; 11: 53-61.
38. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984; 22: 27-55.
39. Berenbaum MC. What is synergy? Pharmacol Rev 1989; 41: 93-141.
40. Tallarida RJ. An overview of drug combination analysis with isobolograms. J Pharmacol Exp Ther 2006; 319: 1-7.
41. Horman S, Galand P, Mosselmans R et al. Changes in the phosphorylation status of the 27 kDa heat shock protein (HSP27) associated with the modulation of growth and/or differentiation in MCF-7 cells. Cell Prolif 1997; 30: 21-35.
42. Horman S, Fokan D, Mosselmans R et al. Anti-sense inhibition of small-heat-shock-protein (HSP27) expression in MCF-7 mammary-carcinoma cells induces their spontaneous acquisition of a secretory phenotype. Int J Cancer 1999: 82: 574-582.
43. Thomas G. p70s6k/p85s6k: Mechanism of activation, effects of rapamycin and role in mitogenesis. Biochem Soc Trans 1993; 21: 901-904.
44. Sugiyama H, Papst P, Gelfand EW, Terada N. p70 S6 kinase sensitivity to rapamycin is eliminated by amino acid substitution of Thr229. J Immunol 1996; 157: 656-660.
45. Ruvinsky I, Meyuhas O. Ribosomal protein S6 phosphorylation: From protein synthesis to cell size. Trends Biochem Sci 2006; 31: 342-348.
46. Rebholz H, Panasyuk G, Fenton T et al. Receptor association and tyrosine phosphorylation of S6 kinases. FEBS J 2006; 273: 2023-2036.
47. Koziczak M, Hynes NE. Cooperation between fibroblast growth factor receptor-4 and ErbB2 in regulation of cyclin D1 translation. J Biol Chem 2004; 279: 50004-50011.
48. Klos KS, Wyszomierski SL, Sun M et al. ErbB2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin/p70S6K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells. Cancer Res 2006; 66: 2028-2037.
49. Johnston SR. Targeting downstream effectors of epidermal growth factor receptor/HER2 in breast cancer with either famesyltransferase inhibitors or mTOR antagonists. Int J Gynecol Cancer 2006; 16 (Suppl 2): 543-548.
50. Mosley JD, Poirier JT, Seachrist DD et al. Rapamycin inhibits multiple stages of c-Neu/ErbB2 induced tumor progression in a transgenic mouse model of HER2-positive breast cancer. Mol Cancer Ther 2007; 6: 2188-2197.
51. Dragowska WH, Verreault M, Yapp DT et al. Decreased levels of hypoxic cells in gefitinib treated ER(+) HER-2 overexpressing MCF-7 breast cancer tumors are associated with hyperactivation of the mTOR pathway: therapeutic implications for combination therapy with rapamycin. Breast Cancer Res Treat 2007; 106: 319-331.
52. Wang LH, Chan JL, Li W. Rapamycin together with herceptin significantly increased anti-tumor efficacy compared to either alone in ErbB2 over expressing breast cancer cells. Int J Cancer 2007; 121: 157-164.
53. Smith BL, Chin D, Maltzman W et al. The efficacy of Herceptin therapies is influenced by the expression of other erbB receptors, their ligands and the activation of downstream signalling proteins. Br J Cancer 2004; 91: 1190-1194.
54. Yu K, Toral-Barza L, Discafani C et al. mTOR, a novel target in breast cancer: The effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Endocr Relat Cancer 2001; 8: 249-258.
55. Chan S, Scheulen ME, Johnston S et al. Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol 2005; 23: 5314-5322.
56. Del Bufalo D, Ciuffreda L, Trisciuoglio D et al. Antiangiogenic potential of the mammalian target of rapamycin inhibitor temsirolimus. Cancer Res 2006; 66: 5549-5554.
57. Chollet P, Abrial C, Tacca O et al. Mammalian target of rapamycin inhibitors in combination with letrozole in breast cancer. Clin Breast Cancer 2006; 7: 336-338.
58. Lane HA, Lebwohl D. Future directions in the treatment of hormone-sensitive advanced breast cancer: The RAD001 (Everolimus)-letrozole clinical program. Semin Oncol 2006; 33 (2 Suppl 7): S18-S25.
59. Boulay A, Zumstein-Mecker S, Stephan C et al. Antitumor efficacy of intermittent treatment schedules with the rapamycin derivative RAD001 correlates with prolonged inactivation of ribosomal protein S6 kinase 1 in peripheral blood mononuclear cells. Cancer Res 2004; 64: 252-261.
60. Sabatini DM. mTOR and cancer: Insights into a complex relationship. Nat Rev Cancer 2006; 6: 729-734.